Infliximab, an inhibitor of TNF, is the standard of care for pediatric patients at least 6 years of age who have corticosteroid-refractory UC or are unable to maintain corticosteroidfree remission on mesalamine.1,2 However, fewer than 40% of patients achieve clinical remission after treatment with the recommended infliximab dosing regimen. Higher infliximab clearance rates may lead to suboptimal therapy, especially in patients with acute UC. To explore this possibility, a prospective study was conducted at 8 centers to determine whether infliximab clearance rates were higher in pediatric patients initially hospitalized with acute severe UC than in patients with less-severe UC.3,4
The study included 37 patients with acute severe UC and 15 with ambulatory UC. In the group with acute severe UC, the median age of the patients was 14.3 years, and 48.6% were female. Extensive disease and/ or pancolitis was noted in 91.9% of the patients, and the mean baseline Pediatric Ulcerative Colitis Activity Index (PUCAI) score was 65. Patients received a median initial dose of infliximab of 9.9 mg/kg. In the ambulatory population, the median age was 15.0 years, and 46.6% of the patients were female. Extensive disease and/or pancolitis was observed in 92.9% of patients, and the mean baseline PUCAI score was 10. Patients in the ambulatory UC group received a median initial dose of infliximab of 5 mg. Predicted infliximab clearance was higher in the acute severe UC cohort than in the ambulatory cohort (P<.01; Figure 4). Modeling also predicted a decrease in infliximab clearance over time.
Figure 4.
The predicted infliximab clearance in the ASUC and the ambulatory cohorts. ASUC, acute severe ulcerative colitis. Adapted from Rosen et al. Abstract 714. Presented at: DDW 2023; May 6-9, 2023; Chicago, Illinois.3
Multivariable linear mixed effects modeling was performed to determine independent variables associated with infliximab clearance at various times from week 0 to week 26 of treatment. Analyses were conducted with pooled data from week 0 to 2, week 2 to 4, week 4 to 8, week 8 to 15, and week 15 to 26. For all times from week 0 to week 15, the infliximab clearance rate was higher in patients whose PUCAI score was 35 or higher, indicating moderately to severely active UC, than in patients whose PUCAI score was 30 or lower, indicating quiescent or mild disease. By weeks 15 to 26, the infliximab clearance rates were similar for the PUCAI subgroups.
References
- Hyams J, Damaraju L, Blank M et al. T72 Study Group. Induction and maintenance therapy with infliximab for children with moderate to severe ulcerative colitis. Clin Gastroenterol Hepatol. 2012;10(4):391–399. doi: 10.1016/j.cgh.2011.11.026. [DOI] [PubMed] [Google Scholar]
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- Rosen MJ, Rabizadeh S, Panetta JC Infliximab clearance in relation to disease activity during induction and maintenance therapy of acute severe and ambulatory pediatric ulcerative colitis. Abstract 714. 2023. Presented at: DDW 2023; May 6-9. Chicago, Illinois. [PMC free article] [PubMed]
- Whaley KG, Xiong Y, Karns R et al. Multicenter cohort study of infliximab pharmacokinetics and therapy response in pediatric acute severe ulcerative colitis. Clin Gastroenterol Hepatol. 2023;21(5):1338–1347. doi: 10.1016/j.cgh.2022.08.016. [DOI] [PMC free article] [PubMed] [Google Scholar]